{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:30:30Z","timestamp":1792801830244,"version":"4.5.0"},"reference-count":109,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005932","name":"Center for Alternatives to Animal Testing","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005932","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["963845"],"award-info":[{"award-number":["963845"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004418","name":"Vrije Universiteit Brussel","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002564","name":"Alternatives Research and Development Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Research Foundation Flanders","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.tox.2025.154263","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T23:22:35Z","timestamp":1755040955000},"page":"154263","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["A mechanistically-anchored and human stem cell-based in vitro test battery for assessing liver steatogenic potential of chemicals"],"prefix":"10.1016","volume":"518","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1275-9498","authenticated-orcid":false,"given":"Anouk","family":"Verhoeven","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7478-3405","authenticated-orcid":false,"given":"Alexandra","family":"Gatzios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robim M.","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julen","family":"Sanz-Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4078-4896","authenticated-orcid":false,"given":"Joery","family":"De Kock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Vinken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6685-7299","authenticated-orcid":false,"given":"Tamara","family":"Vanhaecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tox.2025.154263_bib1","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.3389\/fgene.2019.01007","article-title":"Mining public toxicogenomic data reveals insights and challenges in delineating liver steatosis adverse outcome pathways","volume":"10","author":"AbdulHameed","year":"2019","journal-title":"Front. Genet."},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.bcp.2015.09.004","article-title":"Chemical inhibition of fatty acid absorption and cellular uptake limits lipotoxic cell death","volume":"98","author":"Ahowesso","year":"2015","journal-title":"Biochem. Pharmacol."},{"issue":"5","key":"10.1016\/j.tox.2025.154263_bib3","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.bcp.2009.10.011","article-title":"Inhibition of hepatic carnitine palmitoyl-transferase I (CPT IA) by valproyl-CoA as a possible mechanism of valproate-induced steatosis","volume":"79","author":"Aires","year":"2010","journal-title":"Biochem. Pharmacol."},{"issue":"4","key":"10.1016\/j.tox.2025.154263_bib4","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1177\/0192623314549960","article-title":"Identification of environmental chemicals associated with the development of toxicant associated fatty liver disease in rodents","volume":"43","author":"Al-Eryani","year":"2015","journal-title":"Toxicol. Pathol."},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s10565-020-09537-1","article-title":"Drug-induced hepatic steatosis in absence of severe mitochondrial dysfunction in HepaRG cells: proof of multiple mechanism-based toxicity","volume":"37","author":"Allard","year":"2021","journal-title":"Cell Biol. Toxicol."},{"key":"10.1016\/j.tox.2025.154263_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2019.124519","article-title":"Organophosphorus flame retardant (tricresyl phosphate) trigger apoptosis in HepG2 cells: Transcriptomic evidence on activation of human cancer pathways","volume":"237","author":"Al-Salem","year":"2019","journal-title":"Chemosphere"},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib7","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1093\/toxsci\/kfx121","article-title":"Mechanistic toxicity tests based on an adverse outcome pathway network for hepatic steatosis","volume":"159","author":"Angrish","year":"2017","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"issue":"6","key":"10.1016\/j.tox.2025.154263_bib8","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1002\/hep.24290","article-title":"Induction of vesicular steatosis by amiodarone and tetracycline is associated with up-regulation of lipogenic genes in heparg cells","volume":"53","author":"Anth\u00e9rieu","year":"2011","journal-title":"Hepatology"},{"key":"10.1016\/j.tox.2025.154263_bib9","first-page":"521","article-title":"Adverse outcome pathways as versatile tools in liver toxicity testing","volume":"2425","author":"Arnesdotter","year":"2022"},{"key":"10.1016\/j.tox.2025.154263_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2021.152856","article-title":"Derivation, characterisation and analysis of an adverse outcome pathway network for human hepatotoxicity","volume":"459","author":"Arnesdotter","year":"2021","journal-title":"Toxicology"},{"key":"10.1016\/j.tox.2025.154263_bib11","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jgar.2020.01.022","article-title":"Minocycline, focus on mechanisms of resistance, antibacterial activity, and clinical effectiveness: Back to the future","volume":"22","author":"Asadi","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"issue":"5","key":"10.1016\/j.tox.2025.154263_bib12","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1093\/jac\/dkaf090","article-title":"Population pharmacokinetic model of oral minocycline in critically ill adult patients with ventilator-associated pneumonia","volume":"80","author":"Athanassa","year":"2025","journal-title":"J. Antimicrob. Chemother."},{"key":"10.1016\/j.tox.2025.154263_bib13","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.taap.2017.03.022","article-title":"Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis","volume":"324","author":"Bai","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib14","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12302-019-0195-z","article-title":"Prioritization of hazards of novel flame retardants using the mechanistic toxicology information from ToxCast and adverse outcome pathways","volume":"31","author":"Bajard","year":"2019","journal-title":"Environ. Sci. Eur."},{"issue":"4","key":"10.1016\/j.tox.2025.154263_bib15","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1039\/C6MD00043F","article-title":"Fatty acid transport proteins: targeting FATP2 as a gatekeeper involved in the transport of exogenous fatty acids","volume":"7","author":"Black","year":"2016","journal-title":"MedChemComm"},{"issue":"11","key":"10.1016\/j.tox.2025.154263_bib16","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1021\/acs.estlett.9b00582","article-title":"Organophosphate ester flame retardants: Are they a regrettable substitution for polybrominated diphenyl Ethers?","volume":"6","author":"Blum","year":"2019","journal-title":"Environ. Sci. Technol. Lett."},{"key":"10.1016\/j.tox.2025.154263_bib17","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.phrs.2019.04.016","article-title":"Elafibranor restricts lipogenic and inflammatory responses in a human skin stem cell-derived model of NASH","volume":"144","author":"Boeckmans","year":"2019","journal-title":"Pharmacol. Res."},{"issue":"5","key":"10.1016\/j.tox.2025.154263_bib18","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1111\/liv.15533","volume":"43","author":"Boeckmans","year":"2023","journal-title":"Liver Int."},{"key":"10.1016\/j.tox.2025.154263_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.mex.2020.101068","article-title":"Flow cytometric quantification of neutral lipids in a human skin stem cell-derived model of NASH","volume":"7","author":"Boeckmans","year":"2020","journal-title":"MethodsX"},{"issue":"3","key":"10.1016\/j.tox.2025.154263_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.clinre.2025.102529","article-title":"Mitochondrial dysfunction in drug-induced hepatic steatosis: recent findings and current concept","volume":"49","author":"Borgne-Sanchez","year":"2025","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"10.1016\/j.tox.2025.154263_bib21","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.toxlet.2022.08.006","article-title":"In vitro\/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay","volume":"368","author":"Brecklinghaus","year":"2022","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.tox.2025.154263_bib22","first-page":"1","article-title":"Study of valproic acid-enhanced hepatocyte steatosis","author":"Chang","year":"2016","journal-title":"BioMed Res. Int."},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib23","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/toxsci\/kfv049","article-title":"Increased hepatic fatty acid uptake and esterification contribute to tetracycline-induced steatosis in mice","volume":"145","author":"Choi","year":"2015","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2025.154263_bib24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.toxlet.2017.12.015","article-title":"Metabolomics profiling of steatosis progression in HepaRG \u00ae cells using sodium valproate","volume":"286","author":"Cuykx","year":"2018","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.tox.2025.154263_bib25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.tox.2016.12.007","article-title":"Perfluoroalkyl acids-induced liver steatosis: Effects on genes controlling lipid homeostasis","volume":"378","author":"Das","year":"2017","journal-title":"Toxicology"},{"key":"10.1016\/j.tox.2025.154263_bib26","doi-asserted-by":"crossref","first-page":"481","DOI":"10.18433\/jpps30022","article-title":"Non-alcoholic steatohepatitis (NASH) drug discovery \u2013 building a consensus on ADME Screening tools and clinical pharmacology strategies to aid candidate development","volume":"21","author":"Dash","year":"2018","journal-title":"J. Pharm. Pharm. Sci."},{"key":"10.1016\/j.tox.2025.154263_bib27","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-1-4939-2074-7_8","article-title":"Human skin-derived precursor cells: isolation, expansion, and hepatic differentiation","volume":"1250","author":"De Kock","year":"2015","journal-title":"Methods Mol. Biol."},{"issue":"8","key":"10.1016\/j.tox.2025.154263_bib28","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/j.tiv.2009.08.014","article-title":"Characterization and hepatic differentiation of skin-derived precursors from adult foreskin by sequential exposure to hepatogenic cytokines and growth factors reflecting liver development","volume":"23","author":"De Kock","year":"2009","journal-title":"Toxicol. Vitr."},{"issue":"19","key":"10.1016\/j.tox.2025.154263_bib29","doi-asserted-by":"crossref","first-page":"11428","DOI":"10.3390\/ijms231911428","article-title":"In vitro models for studying chronic drug-induced liver injury","volume":"23","author":"Donato","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.tox.2025.154263_bib30","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.diff.2019.02.004","article-title":"Stem-cell derived hepatocyte-like cells for the assessment of drug-induced liver injury","volume":"106","author":"Donato","year":"2019","journal-title":"Differentiation"},{"key":"10.1016\/j.tox.2025.154263_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2022.116136","article-title":"In vitro activity of a panel of per- and polyfluoroalkyl substances (PFAS), fatty acids, and pharmaceuticals in peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma, and estrogen receptor assays","volume":"449","author":"Evans","year":"2022","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"3","key":"10.1016\/j.tox.2025.154263_bib32","doi-asserted-by":"crossref","first-page":"E384","DOI":"10.1152\/ajpendo.00226.2010","article-title":"FATP2 is a hepatic fatty acid transporter and peroxisomal very long-chain acyl-CoA synthetase","volume":"299","author":"Falcon","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib33","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/toxres\/tfaa011","article-title":"Toxicity testing is evolving!","volume":"9","author":"Fischer","year":"2020","journal-title":"Toxicol. Res."},{"key":"10.1016\/j.tox.2025.154263_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.crtox.2025.100238","article-title":"Hepatocytes derived from human induced pluripotent stem cells: towards establishing an in vitro model for assessing population variability in hepatotoxicity testing","volume":"8","author":"Gao","year":"2025","journal-title":"Curr. Res. Toxicol."},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3390\/biomedicines10010161","article-title":"From NAFLD to MAFLD: aligning translational in vitro research to clinical insights","volume":"10","author":"Gatzios","year":"2022","journal-title":"Biomedicines"},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib36","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1002\/hep.28886","article-title":"Stem cell-derived models to improve mechanistic understanding and prediction of human drug induced liver injury","volume":"65","author":"Goldring","year":"2017","journal-title":"Hepatology"},{"key":"10.1016\/j.tox.2025.154263_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2020.113860","article-title":"Valproic acid affects fatty acid and triglyceride metabolism in HepaRG cells exposed to fatty acids by different mechanisms","volume":"177","author":"Gr\u00fcnig","year":"2020","journal-title":"Biochem. Pharmacol."},{"issue":"11","key":"10.1016\/j.tox.2025.154263_bib38","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1007\/s00204-020-02868-2","article-title":"Screening of repeated dose toxicity data in safety evaluation reports of cosmetic ingredients issued by the scientific committee on consumer safety between 2009 and 2019","volume":"94","author":"Gustafson","year":"2020","journal-title":"Arch. Toxicol."},{"issue":"6","key":"10.1016\/j.tox.2025.154263_bib39","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1021\/acs.chemrestox.9b00058","article-title":"Organophosphorus flame retardants impair intracellular lipid metabolic function in human hepatocellular cells","volume":"32","author":"Hao","year":"2019","journal-title":"Chem. Res. Toxicol."},{"issue":"10","key":"10.1016\/j.tox.2025.154263_bib40","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1258\/ebm.2011.011128","article-title":"The emerging roles of fatty acid translocase\/CD36 and the aryl hydrocarbon receptor in fatty liver disease","volume":"236","author":"He","year":"2011","journal-title":"Exp. Biol. Med."},{"issue":"11","key":"10.1016\/j.tox.2025.154263_bib41","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1007\/s00204-014-1336-1","article-title":"Hepatotoxic effects of (tri)azole fungicides in a broad dose range","volume":"89","author":"Heise","year":"2015","journal-title":"Arch. Toxicol."},{"issue":"12","key":"10.1016\/j.tox.2025.154263_bib42","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41574-019-0256-9","article-title":"The regulation of hepatic fatty acid synthesis and partitioning: the effect of nutritional state","volume":"15","author":"Hodson","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"issue":"9","key":"10.1016\/j.tox.2025.154263_bib43","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1124\/dmd.114.059154","article-title":"Long-term chronic toxicity testing using human pluripotent stem cell-derived hepatocytes","volume":"42","author":"Holmgren","year":"2014","journal-title":"Drug Metab. Dispos."},{"issue":"10464","key":"10.1016\/j.tox.2025.154263_bib44","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/S0140-6736(24)01811-7","article-title":"Steatotic liver disease","volume":"404","author":"Israelsen","year":"2024","journal-title":"Lancet"},{"issue":"12","key":"10.1016\/j.tox.2025.154263_bib45","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1007\/s00204-014-1410-8","article-title":"SEURAT-1 liver gold reference compounds: a mechanism-based review","volume":"88","author":"Jennings","year":"2014","journal-title":"Arch. Toxicol."},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib46","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13287-021-02152-9","article-title":"Advancements in stem cell-derived hepatocyte-like cell models for hepatotoxicity testing","volume":"12","author":"Jin","year":"2021","journal-title":"Stem Cell Res. Ther."},{"issue":"4","key":"10.1016\/j.tox.2025.154263_bib47","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1039\/c7tx00326a","article-title":"Role of xenobiotics in the induction and progression of fatty liver disease","volume":"7","author":"Klaunig","year":"2018","journal-title":"Toxicol. Res."},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib48","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/apt.18059","article-title":"Review article: hepatic steatosis and its associations with acute and chronic liver diseases","volume":"60","author":"Koenig","year":"2024","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"8","key":"10.1016\/j.tox.2025.154263_bib49","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1007\/s00204-019-02501-x","article-title":"Characterizing the coverage of critical effects relevant in the safety evaluation of food additives by AOPs","volume":"93","author":"Kramer","year":"2019","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.tox.2025.154263_bib50","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1126880","article-title":"Development of a reference and proficiency chemical list for human steatosis endpoints in vitro","volume":"14","author":"Kubickova","year":"2023","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.tox.2025.154263_bib51","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.tiv.2018.01.023","article-title":"Impact of cell types and culture methods on the functionality of in vitro liver systems \u2013 a review of cell systems for hepatotoxicity assessment","volume":"48","author":"Kyffin","year":"2018","journal-title":"Toxicol. Vitr."},{"issue":"4","key":"10.1016\/j.tox.2025.154263_bib52","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s00204-020-02685-7","article-title":"Combinations of LXR and RXR agonists induce triglyceride accumulation in human HepaRG cells in a synergistic manner","volume":"94","author":"Lasch","year":"2020","journal-title":"Arch. Toxicol."},{"issue":"11","key":"10.1016\/j.tox.2025.154263_bib53","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1007\/s00204-017-2045-3","article-title":"Adverse outcome pathways: opportunities, limitations and open questions","volume":"91","author":"Leist","year":"2017","journal-title":"Arch. Toxicol."},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib54","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1053\/jhep.2003.50309","article-title":"Inhibition of microsomal triglyceride transfer protein: Another mechanism for drug-induced steatosis in mice","volume":"38","author":"Lett\u00e9ron","year":"2003","journal-title":"Hepatology"},{"key":"10.1016\/j.tox.2025.154263_bib55","doi-asserted-by":"crossref","DOI":"10.1016\/j.fct.2020.111283","article-title":"An adverse outcome pathway-based approach to assess steatotic mixture effects of hepatotoxic pesticides in vitro","volume":"139","author":"Lichtenstein","year":"2020","journal-title":"Food Chem. Toxicol."},{"issue":"4","key":"10.1016\/j.tox.2025.154263_bib56","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time guantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"issue":"10","key":"10.1016\/j.tox.2025.154263_bib57","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1016\/j.bbamcr.2016.01.023","article-title":"Carnitine transport and fatty acid oxidation","volume":"1863","author":"Longo","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"issue":"10","key":"10.1016\/j.tox.2025.154263_bib58","doi-asserted-by":"crossref","first-page":"5203","DOI":"10.3390\/ijms25105203","article-title":"Drug-induced fatty liver disease (DIFLD): a comprehensive analysis of clinical, biochemical, and histopathological data for mechanisms identification and consistency with current adverse outcome pathways","volume":"25","author":"L\u00f3pez-Pascual","year":"2024","journal-title":"Int. J. Mol. Sci."},{"issue":"4","key":"10.1016\/j.tox.2025.154263_bib59","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s00204-023-03450-2","article-title":"Determination of in vitro hepatotoxic potencies of a series of perfluoroalkyl substances (PFASs) based on gene expression changes in HepaRG liver cells","volume":"97","author":"Louisse","year":"2023","journal-title":"Arch. Toxicol."},{"issue":"8","key":"10.1016\/j.tox.2025.154263_bib60","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1021\/acs.chemrestox.8b00112","article-title":"Adverse outcome pathway-driven analysis of liver steatosis in vitro: a case study with cyproconazole","volume":"31","author":"Luckert","year":"2018","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.tox.2025.154263_bib61","article-title":"Variability in in vivo studies: defining the upper limit of performance for predictions of systemic effect levels","volume":"15","author":"Ly Pham","year":"2020","journal-title":"Comput. Toxicol."},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1517\/17425255.2015.981523","article-title":"Human induced pluripotent stem cell-derived hepatocytes for toxicology testing","volume":"11","author":"Mann","year":"2015","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"10.1016\/j.tox.2025.154263_bib63","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2022.115991","article-title":"Replacement per- and polyfluoroalkyl substances (PFAS) are potent modulators of lipogenic and drug metabolizing gene expression signatures in primary human hepatocytes","volume":"442","author":"Marques","year":"2022","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"8","key":"10.1016\/j.tox.2025.154263_bib64","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1007\/s00204-016-1925-2","article-title":"Hepatotoxic effects of cyproconazole and prochloraz in wild-type and hCAR\/hPXR mice","volume":"91","author":"Marx-Stoelting","year":"2017","journal-title":"Archives of Toxicology"},{"issue":"5","key":"10.1016\/j.tox.2025.154263_bib65","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.3390\/cells9051192","article-title":"The connection of azole fungicides with xeno-sensing nuclear receptors, drug metabolism and hepatotoxicity","volume":"9","author":"Marx-Stoelting","year":"2020","journal-title":"Cells"},{"issue":"6","key":"10.1016\/j.tox.2025.154263_bib66","doi-asserted-by":"crossref","first-page":"697","DOI":"10.3945\/an.113.004648","article-title":"Hepatic fatty acid trafficking: multiple forks in the road123","volume":"4","author":"Mashek","year":"2013","journal-title":"Adv. Nutr."},{"issue":"3","key":"10.1016\/j.tox.2025.154263_bib67","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/01.mol.0000226119.20307.2b","article-title":"Cellular fatty acid uptake: the contribution of metabolism","volume":"17","author":"Mashek","year":"2006","journal-title":"Curr. Opin. Lipidol."},{"issue":"3","key":"10.1016\/j.tox.2025.154263_bib68","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1124\/jpet.104.072785","article-title":"Disruption of hepatic lipid homeostasis in mice after amiodarone treatment is associated with peroxisome proliferator-activated receptor-alpha target gene activation","volume":"311","author":"McCarthy","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib69","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3109\/10408444.2015.1089471","article-title":"The identification of nuclear receptors associated with hepatic steatosis to develop and extend adverse outcome pathways","volume":"46","author":"Mellor","year":"2016","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.tox.2025.154263_bib70","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.toxlet.2017.11.014","article-title":"Hepatic cells derived from human skin progenitors show a typical phospholipidotic response upon exposure to amiodarone","volume":"284","author":"Natale","year":"2018","journal-title":"Toxicol. Lett."},{"issue":"7","key":"10.1016\/j.tox.2025.154263_bib71","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1007\/s00204-019-02465-y","article-title":"Technological advancements for the development of stem cell-based models for hepatotoxicity testing","volume":"93","author":"Natale","year":"2019","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.tox.2025.154263_bib72","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2021.117855","article-title":"An adverse outcome pathway based in vitro characterization of novel flame retardants-induced hepatic steatosis","volume":"289","author":"Negi","year":"2021","journal-title":"Environ. Pollut."},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib73","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1006\/rtph.2000.1399","article-title":"Concordance of the toxicity of pharmaceuticals in humans and in animals","volume":"32","author":"Olson","year":"2000","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"6","key":"10.1016\/j.tox.2025.154263_bib74","doi-asserted-by":"crossref","first-page":"4413","DOI":"10.1074\/jbc.M107460200","article-title":"The late addition of core lipids to nascent apolipoprotein B100, resulting in the assembly and secretion of triglyceride-rich lipoproteins, is independent of both microsomal triglyceride transfer protein activity and new triglyceride synthesis","volume":"277","author":"Pan","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.tox.2025.154263_bib75","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2020.152493","article-title":"Mechanism-based identification of plasma metabolites associated with liver toxicity","volume":"441","author":"Pannala","year":"2020","journal-title":"Toxicology"},{"key":"10.1016\/j.tox.2025.154263_bib76","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2024.176668","article-title":"Tartaric acid ameliorates experimental non-alcoholic fatty liver disease by activating the AMP-activated protein kinase signaling pathway","volume":"975","author":"Pei","year":"2024","journal-title":"Eur. J. Pharmacol."},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib77","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/toxsci\/kfaa148","article-title":"Perfluorooctanesulfonic acid and perfluorohexanesulfonic acid alter the blood lipidome and the hepatic proteome in a murine model of diet-induced obesity","volume":"178","author":"Pfohl","year":"2020","journal-title":"Toxicol. Sci."},{"issue":"1\u20132","key":"10.1016\/j.tox.2025.154263_bib78","first-page":"1","article-title":"Role of FATP in parenchymal cell fatty acid uptake","volume":"1686","author":"Pohl","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib79","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1079\/PNS2004341","article-title":"New concepts of cellular fatty acid uptake: role of fatty acid transport proteins and of caveolae","volume":"63","author":"Pohl","year":"2004","journal-title":"Proc. Nutr. Soc."},{"issue":"9","key":"10.1016\/j.tox.2025.154263_bib80","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/s41419-020-03003-w","article-title":"Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?","volume":"11","author":"Rada","year":"2020","journal-title":"Cell Death Dis."},{"issue":"3","key":"10.1016\/j.tox.2025.154263_bib81","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s00204-015-1483-z","article-title":"In vitro assessment of drug-induced liver steatosis based on human dermal stem cell-derived hepatic cells","volume":"90","author":"Rodrigues","year":"2016","journal-title":"Arch. Toxicol."},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib82","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1089\/scd.2013.0157","article-title":"Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity screening of pharmaceuticals","volume":"23","author":"Rodrigues","year":"2014","journal-title":"Stem Cells Dev."},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib83","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00204-014-1199-5","article-title":"Human stem cell-derived hepatocytes: breakthrough of an expedient tool for preclinical assessment of drug-induced liver injury?","volume":"88","author":"Rodrigues","year":"2014","journal-title":"Arch. Toxicol."},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib84","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.toxlet.2015.10.014","article-title":"Toxicogenomics-based prediction of acetaminophen-induced liver injury using human hepatic cell systems","volume":"240","author":"Rodrigues","year":"2016","journal-title":"Toxicol. Lett."},{"issue":"6","key":"10.1016\/j.tox.2025.154263_bib85","doi-asserted-by":"crossref","first-page":"3486","DOI":"10.1002\/hep.31999","article-title":"Key characteristics of human hepatotoxicants as a basis for identification and characterization of the causes of liver toxicity","volume":"74","author":"Rusyn","year":"2021","journal-title":"Hepatology"},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib86","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00204-023-03649-3","article-title":"Impact of perfluoroalkyl substances (PFAS) and PFAS mixtures on lipid metabolism in differentiated HepaRG cells as a model for human hepatocytes","volume":"98","author":"Sadrabadi","year":"2024","journal-title":"Arch. Toxicol."},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib87","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/brv.12178","article-title":"De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose","volume":"91","author":"Sanders","year":"2016","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"10.1016\/j.tox.2025.154263_bib88","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2023.108082","article-title":"New approach methodologies in human regulatory toxicology \u2013 not if, but how and when!","volume":"178","author":"Schmeisser","year":"2023","journal-title":"Environ. Int."},{"issue":"356","key":"10.1016\/j.tox.2025.154263_bib89","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.tox.2016.05.018","article-title":"Combination effects of azole fungicides in male rats in a broad dose range","volume":"355","author":"Schmidt","year":"2016","journal-title":"Toxicology"},{"issue":"22","key":"10.1016\/j.tox.2025.154263_bib90","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1101\/gad.850400","article-title":"Role of LXRs in control of lipogenesis","volume":"14","author":"Schultz","year":"2000","journal-title":"Genes Dev."},{"key":"10.1016\/j.tox.2025.154263_bib91","doi-asserted-by":"crossref","DOI":"10.1016\/j.yrtph.2025.105794","article-title":"Next generation risk assessment of hair dye HC yellow no. 13: ensuring protection from liver steatogenic effects","volume":"159","author":"Sepehri","year":"2025","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"5","key":"10.1016\/j.tox.2025.154263_bib92","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1007\/s10620-016-4054-0","article-title":"Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease","volume":"61","author":"Softic","year":"2016","journal-title":"Dig. Dis. Sci."},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib93","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1039\/C2TX20051A","article-title":"In vitro models for liver toxicity testing","volume":"2","author":"Soldatow","year":"2013","journal-title":"Toxicol. Res."},{"issue":"2","key":"10.1016\/j.tox.2025.154263_bib94","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.tem.2008.11.001","article-title":"Cellular fatty acid uptake: a pathway under construction","volume":"20","author":"Su","year":"2009","journal-title":"Trends Endocrinol. Metab. TEM"},{"issue":"1","key":"10.1016\/j.tox.2025.154263_bib95","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0086795","article-title":"Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices","volume":"9","author":"Szalowska","year":"2014","journal-title":"PLOS One"},{"issue":"1\u20132","key":"10.1016\/j.tox.2025.154263_bib96","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11010-005-9041-2","article-title":"Characterization of a BODIPY-labeled fluorescent fatty acid analogue. Binding to fatty acid-binding proteins, intracellular localization, and metabolism","volume":"299","author":"Thumser","year":"2007","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.tox.2025.154263_bib97","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.tox.2017.11.013","article-title":"Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction","volume":"393","author":"van Breda","year":"2018","journal-title":"Toxicology"},{"key":"10.1016\/j.tox.2025.154263_bib98","series-title":"Toxicogenomics-Based Cellular Models","first-page":"193","article-title":"Hepatotoxicity screening on in vitro models and the role of omics","author":"Van Delft","year":"2014"},{"issue":"7","key":"10.1016\/j.tox.2025.154263_bib99","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jacbts.2019.10.008","article-title":"Limitations of animal studies for predicting toxicity in clinical trials","volume":"4","author":"Van Norman","year":"2019","journal-title":"JACC Basic Translational Science"},{"key":"10.1016\/j.tox.2025.154263_bib100","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2024.153814","article-title":"A quantitative weight-of-evidence method for confidence assessment of adverse outcome pathway networks: a case study on chemical-induced liver steatosis","volume":"505","author":"Verhoeven","year":"2024","journal-title":"Toxicology"},{"key":"10.1016\/j.tox.2025.154263_bib101","article-title":"Adverse outcome pathway networks as the basis for the development of new approach methodologies: liver toxicity as a case study","volume":"40","author":"Vinken","year":"2024","journal-title":"Curr. Opin. Toxicol."},{"issue":"3","key":"10.1016\/j.tox.2025.154263_bib102","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1002\/hep.24148","article-title":"Nuclear receptors in liver disease","volume":"53","author":"Wagner","year":"2011","journal-title":"Hepatology"},{"issue":"3","key":"10.1016\/j.tox.2025.154263_bib103","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s40572-019-00232-w","article-title":"Mechanisms of environmental contributions to fatty liver disease","volume":"6","author":"Wahlang","year":"2019","journal-title":"Curr. Environ. Health Rep."},{"key":"10.1016\/j.tox.2025.154263_bib104","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.biochi.2013.08.022","article-title":"Metabolic functions of peroxisomes in health and disease","volume":"98","author":"Wanders","year":"2014","journal-title":"Biochimie"},{"key":"10.1016\/j.tox.2025.154263_bib105","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2020.105946","article-title":"Review of emerging contaminant tris(1,3-dichloro-2-propyl)phosphate: Environmental occurrence, exposure, and risks to organisms and human health","volume":"143","author":"Wang","year":"2020","journal-title":"Environ. Int."},{"key":"10.1016\/j.tox.2025.154263_bib106","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.plipres.2015.05.002","article-title":"Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research","volume":"59","author":"Willebrords","year":"2015","journal-title":"Prog. Lipid Res."},{"issue":"41","key":"10.1016\/j.tox.2025.154263_bib107","doi-asserted-by":"crossref","first-page":"7254","DOI":"10.1021\/bi400914c","article-title":"CD36 enhances fatty acid uptake by increasing the rate of intracellular esterification but not transport across the plasma membrane","volume":"52","author":"Xu","year":"2013","journal-title":"Biochemistry"},{"key":"10.1016\/j.tox.2025.154263_bib108","article-title":"CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing","volume":"57","author":"Zeng","year":"2021","journal-title":"Mol. Metab."},{"issue":"11","key":"10.1016\/j.tox.2025.154263_bib109","doi-asserted-by":"crossref","first-page":"802","DOI":"10.3390\/toxins13110802","article-title":"Ochratoxin a induces steatosis via PPAR\u03b3-CD36 axis","volume":"13","author":"Zheng","year":"2021","journal-title":"Toxins"}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X25002227?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X25002227?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T14:59:03Z","timestamp":1772809143000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X25002227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":109,"alternative-id":["S0300483X25002227"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2025.154263","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A mechanistically-anchored and human stem cell-based in vitro test battery for assessing liver steatogenic potential of chemicals","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2025.154263","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"154263"}}